This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This protein is usually called CRP. This can stand for "cAMP receptor protein" OR catabolite repressor protein". In E. coli the homolog was solved about 20 years ago by Steitz etal, and has become a textbook lesson in gene regulation because it *binds cAMP *then binds DNA at many repressors *shuts off several sugar-utilization pathways *bends the DNA where it binds. The present project is CRP from Mycobacterium tuberculosis. It is 30% identical but Molec Replacement has failed. Why pursue the structure of this homolog? In Mt, the functions are not identical;there are more genetic effects than in Ecoli. Also, Mt is an important pathogen target. Also, the previous work in Ecoli has failed to give a structure of the unliganded protein. We have crystallized the unliganded form, along with liganded forms. We have crystallized the protein in three forms: unliganded, with cAMP, and with cAMP and DNA. We hope to see the structure in all 3 forms and assess conformational changes. This will advance the fields of transcription and gene regulation in structural biology, and also provide data on tuberculosis pathogens.